MICRODAMAGE, OSTEOCYTE INTEGRITY AND BONE REMODELING

据推测，骨性重塑用于去除和 替换致密骨中积累微损伤的区域 由于疲劳。然而，人们对损失或 在预期的疲劳水平上发生的重塑反应 由于正常的磨损而导致。骨骼重塑单位 显微镜下骨骼受损的“靶区”尚不清楚。 有效的靶向和移除受损的骨骼对于 保持骨骼的完整性。最近的数据表明， 早期以超微结构水平的骨基质损伤为主 人体骨骼的疲劳过程，而不是典型的线性 被广泛认为代表原生生物的微裂纹 疲劳过程。这种主要的疲劳损伤的作用 激活皮质内重塑过程的模式是 目前还未被开发。使用我们的尺骨弯曲改良术 Torrance等(112)建立的成年大鼠尺骨疲劳模型 活体，以启动皮质内吸收活动。研究亦包括 提示骨细胞活力的降低会随着疲劳和 损伤，骨细胞完整性改变的区域可以 与皮质内吸收相关，独立于 微损伤。拟议的研究将审查a)是否 骨启动早期超微结构水平的疲劳损伤 皮质内重建，b)骨疲劳如何影响骨细胞 完整性，以及c)骨细胞完整性的改变是否 皮质内重构的决定因素。具体地说，我们将使用 三个相关实验的大鼠尺骨疲劳模型： 1)体内疲劳负荷，结合共聚焦显微镜 骨组织形态计量学将用于确定颞骨 和矩阵级别损伤过程的空间关联 皮质内重塑。 2)我们将确定骨基质的特定结合 微损伤与骨细胞活性或骨细胞损伤/丢失 生存能力，并检查骨细胞 在疲劳负荷下，骨骼会发生退变。骨细胞完整性 相对于局部骨损伤状态将使用新的 成骨细胞活性原位检测方法的发展 (与受伤的、不能存活的细胞相比)。一种就地组合 细胞化学染色技术和电子显微镜将 二次用于评价骨细胞的作用机制 退化。一个具体的焦点将是 细胞凋亡是骨细胞对疲劳反应的特征。 3)我们将确定时空关联 皮质内吸收和存活/不存活的骨细胞之间的关系 结合前人对蟑螂的研究。

It is postulated that osteonal remodeling serves to remove and replace regions of compact bone which accumulate microdamage due to fatigue. However, little is known about the damage or remodeling responses which occur at the levels of fatigue expected to result from normal wear and tear. How bone remodeling units "target" microscopically damaged areas of bone is unknown. Effective targeting and removal of damaged bone is essential for maintaining skeletal integrity. Recent data indicates that ultrastructural-level bone matrix damage dominates the early fatigue process in human bone, rather than the typical linear microcracks which have been widely thought to represent primary fatigue process. The role of this predominant fatigue damage mode on activation of intracortical remodeling processes is currently unexplored. Using our modification of the ulnar bending model of Torrance et al (112), adult rat ulnae can be fatigued in vivo, to initiate intracortical resorption activity. Studies also suggest that decreased osteocyte viability occurs with fatigue and injury, and that areas of altered osteocyte integrity can be associated with intracortical resorption, independent Of microdamage. The proposed studies will examine a) whether early, ultrastructural level fatigue damage in bone initiate intracortical remodeling, b) how bone fatigue affects osteocyte integrity, and c) whether changes in osteocyte integrity are a determinant of intracortical remodeling. Specifically, we will use the rat ulnar fatigue model for three interrelated experiments: 1) In vivo fatigue loading, combined with confocal microscopy and bone histomorphometry will be used to determine temporal and spatial associations of matrix-level damage processes with intracortical remodeling. 2) We will determine the specific associations of bone matrix microdamage and osteocyte viability or osteocyte injury/loss of viability, and examine the mechanism by which osteocyte degeneration occurs in fatigue loaded bone. Osteocyte integrity relative to local bone damage state will be assessed using a newly developed methods for in situ detection of osteocyte viability (versus injured, nonviable cells). A combination of in situ cytochemical staining techniques and electron microscopy will be used secondarily to assess the mechanism of osteocyte degeneration. A specific focus will be on the question of whether apoptosis is characteristic of the response of osteocytes to fatigue. 3) We will determine the spatial and temporal associations between intracortical resorption and viable/nonviable osteocytes by combinin a roaches from the recedin studies.